Intact antibodies (immunoglobulins IgG, IgM, IgA, and IgE) are highly specific targeting reagents that form part of our key defense against pathogens and toxins.
IgG, the main serum antibody, the intact form of which is almost exclusively used in therapeutic antibodies, is a Y-shaped, multidomain protein with antigen-binding sites located on the two Fab (antigen-binding fragment) tips and effector functions mediated by the stem Fc (crystallizable fragment) domain (see Figure).
There is a range of applications for which the Fc-mediated effects are neither required nor are desirable.
Inappropriate activation of the Fc receptor-expressing cells by antibodies can lead to cytokine release and toxicity.